Chordoma Foundation

Neurosurgeon seeks to utilize the immune system against chordoma

For the past 10 years, Dr. Michael Lim’s position at Johns Hopkins University School of Medicine in Baltimore has required him to balance the duties of both a clinician and a researcher. A skilled neurosurgeon specializing in primary and metastatic brain tumors, his calm demeanor belies the urgency with which he tackles every task, whether in the operating room or the lab.

At Hopkins, Dr. Lim is known by his impressive string of appointments, including associate professor of Neurosurgery, Oncology, Radiation Oncology, and Radiation Molecular Sciences, director of the Brain Tumor Immunotherapy Program, director of the Metastatic Brain Tumor Center, and director of the Ependymoma/Subependymoma Center. At the Chordoma Foundation, we know him for his fierce dedication to improving the lives of chordoma patients, and for his tireless efforts to determine how effective immunotherapy could be in fighting the disease.

As the body’s first line of defense against disease, the immune system should be an important factor in protection from cancer. However, over the years, scientists have found that cancer evades our natural defenses by commandeering a normal protective mechanism: proteins on a cell’s surface called immune checkpoints, which act as brakes on the immune system. We now know that some cancers cloak themselves in these checkpoint proteins, evading the immune system and allowing unchecked growth.

This knowledge has led to the development of checkpoint inhibitors – drugs that release the brakes that cancer cells put on the immune system, thereby enabling the body’s immune system to more effectively fight the cancer. Checkpoint inhibitors are already approved to treat certain types of cancers, including melanoma, lung, kidney, bladder, head and neck, and blood. And currently, hundreds of clinical trials are underway testing new and approved immunotherapies in an array of other cancer types. Since 2011, the Chordoma Foundation has supported Dr. Lim’s research investigating the potential to these checkpoint inhibitors to treat chordoma.

First, Dr. Lim and his team set out to see whether chordomas, like some other cancers, evade the immune system by expressing checkpoint proteins. The results of this research, published in January 2015 in the Journal of Neuro-Oncology, confirmed the proteins were present in 10 chordoma tissue samples. Next, Dr. Lim and his team set out to test whether a checkpoint inhibitor could generate an anti-tumor response in mice. This required them to develop a new type of mouse model with a functional human immune system – as opposed to the immune deficient mouse models that are typically used for laboratory experiments.

“We wanted to use a more relevant model to study immunotherapies in chordoma,” says Lim. “We have learned that just testing drugs on cancer cells is not fully representative of what is going on in the body. It’s really the immune system that is the treatment and the immunotherapy acts on the immune system. In order to assess the efficacy of different immunotherapy strategies, you need for the mouse model to have an intact functional immune system. There is a whole choreographed event that happens with the immune system to get an anti-tumor immune response.”

lim_blog_photo2This research has not yet been published. But, says Lim, “the preliminary data suggest potential for an anti PD-1 drug to be an effective therapy for chordoma.” With the support of the Chordoma Foundation, Dr. Lim and his collaborator at Memorial Sloan Kettering, Dr. Josh Yamada, plan to launch the first-ever checkpoint inhibitor trial in chordomas. The trial, which is expected to begin enrolling patients later this year, will test a drug called nivolumab (Opdivo) in combination with hypofractionated radiation in patients with advanced recurrent chordoma.

“We take care of a lot of patients with chordoma at Johns Hopkins, and we’ve seen a lot of patients suffering with this disease. We want to look beyond what we have as the current standard of care and see what we can do better.”

A team player, Dr. Lim is quick to point out that his efforts to advance chordoma research are tied to and supported by all of the members of the neurosurgery group at Johns Hopkins. The breadth and strength of the Johns Hopkins team, he says, “gives each of us the ability to be specialists in what we do,” which benefits all patients with tumors in the skull, brain, or spine.

Most importantly, says Lim, “credit goes to the Foundation’s Executive Director Josh Sommer. In him, we have an amazing patient advocate. He is passionate about this work and the progress we have made in this field is due to him. He has found ways to get new researchers to focus on chordoma. And the more minds we have in this, the better are our chances of finding a cure.”


Stay tuned for more details about trial enrollment, coming soon. You can join our efforts to bring better treatment options to those affected by chordoma by donating today. Contact Josh Sommer, josh@chordoma.org, with questions about making a donation.